Novartis Reports Positive Phase III Results for Remibrutinib in Relapsing Multiple Sclerosis

REMODEL-1 and REMODEL-2 Trials Show Lower Relapse Rates

Novartis has announced positive topline results from its Phase III REMODEL-1 and REMODEL-2 trials evaluating remibrutinib in adults with relapsing multiple sclerosis (RMS).

The investigational treatment is an oral Bruton’s tyrosine kinase (BTK) inhibitor designed to target immune pathways involved in multiple sclerosis.

In both Phase III studies, remibrutinib performed better than teriflunomide in reducing annualized relapse rate (ARR) and inflammatory brain lesions.

The trials also showed clinically meaningful results on measures related to disability progression. The safety profile remained favourable, with no liver safety signal identified during the studies.

Novartis plans to present detailed data from the REMODEL-1 and REMODEL-2 trials as a late-breaking presentation at MSToronto2026. The company also plans to seek regulatory approval for remibrutinib as a treatment for RMS in markets around the world.

Remibrutinib Shows Superiority Over Teriflunomide

The main goal of the REMODEL-1 and REMODEL-2 trials was to compare remibrutinib with teriflunomide in people with RMS.

The primary endpoint for both studies was annualized relapse rate.

The topline results showed that remibrutinib was superior to teriflunomide in reducing the annualized relapse rate across both Phase III trials.

This is an important measure in relapsing multiple sclerosis because relapses can lead to new symptoms and, in some cases, contribute to long-term disability.

The studies also found reductions in inflammatory brain lesions, providing additional evidence that remibrutinib can affect disease activity in the central nervous system.

Results Also Point to Slower Disability Progression

The trials included several secondary measures looking at disability progression.

In a preplanned combined analysis of REMODEL-1 and REMODEL-2, remibrutinib showed a positive trend in 3-month confirmed disability progression, known as 3mCDP.

The treatment also achieved nominal statistical significance for 6-month confirmed disability progression, or 6mCDP.

These findings suggest that the potential benefit of remibrutinib may extend beyond reducing relapses.

Disability progression is an important concern for people living with multiple sclerosis because the disease can gradually affect mobility, coordination, vision and other neurological functions.

The longer-term extension periods of the trials are expected to provide additional information about how remibrutinib affects disease progression over time.

What Is Remibrutinib?

Remibrutinib is an oral BTK inhibitor discovered by Novartis.

The medicine works by blocking the BTK pathway, which plays a role in the activation of B cells and certain innate immune cells.

By affecting these immune cells and related signaling pathways, remibrutinib is designed to modify immune activity and reduce neuroinflammation.

This approach is different from simply treating the symptoms of multiple sclerosis. The goal is to interfere with immune processes that contribute to disease activity.

Novartis is studying remibrutinib across several conditions. Its development program includes neuroscience and immune-mediated diseases.

In multiple sclerosis, the company is evaluating the medicine in RMS through the REMODEL program and in secondary progressive multiple sclerosis through the Phase III REMASTER study.

Safety Profile Remains Favourable

Safety is a major consideration when developing long-term treatments for multiple sclerosis.

According to Novartis, the safety profile observed in REMODEL-1 and REMODEL-2 was consistent with the broader clinical development program for remibrutinib.

More than 4,500 participants have been included in clinical trials of remibrutinib across different indications.

The company reported that remibrutinib was well tolerated in the REMODEL studies.

Importantly, Novartis said there was no liver safety signal associated with the treatment. No cases meeting Hy’s Law criteria were reported.

Hy’s Law is used in clinical development to identify potential serious drug-induced liver injury.

The absence of such a signal is relevant because RMS treatments may be used for many years, making long-term safety an important part of the benefit-risk assessment.

Understanding Relapsing Multiple Sclerosis

Multiple sclerosis is a chronic inflammatory disease that affects the central nervous system.

The disease can damage myelin, the protective covering around nerve fibres, as well as the axons themselves. This damage can occur in areas such as the brain, optic nerves and spinal cord.

Multiple sclerosis affects nearly 3 million people worldwide.

The disease can appear in different forms. These include primary progressive multiple sclerosis, non-active secondary progressive multiple sclerosis and relapsing multiple sclerosis.

Relapsing multiple sclerosis is the most common form.

RMS includes clinically isolated syndrome, relapsing-remitting multiple sclerosis and active secondary progressive multiple sclerosis.

People with RMS can experience periods of worsening symptoms, known as relapses, followed by periods when symptoms improve or remain stable.

Over time, some people may also develop increasing disability.

Why Relapse Prevention Matters

A relapse can cause new neurological symptoms or make existing symptoms worse.

Symptoms can vary from person to person and may include problems with vision, movement, balance, sensation or coordination.

Preventing relapses is therefore an important part of RMS treatment.

At the same time, controlling inflammatory disease activity may not be enough if disability continues to progress.

This is why the REMODEL trials looked at both relapse activity and disability progression.

The positive results across these measures could support further evaluation of remibrutinib as an oral treatment option for people with RMS.

How the REMODEL Trials Were Designed

REMODEL-1 and REMODEL-2 are identical multicenter, randomized, double-blind, active-comparator controlled Phase III studies.

Together, the trials enrolled approximately 2,000 patients globally.

Participants were adults with relapsing multiple sclerosis who had evidence of recent disease activity.

Eligible participants had an Expanded Disability Status Scale score ranging from 0.0 to 5.5.

Patients were randomly assigned in a 1:1 ratio to receive either remibrutinib 100 mg or teriflunomide.

The initial double-blind core portion of each study has a flexible duration of up to 30 months.

After the core period, participants can enter an open-label extension lasting for up to five years.

This longer follow-up is designed to provide more information about the treatment's long-term effectiveness and safety.

Additional Measures Used in the Studies

Annualized relapse rate was the primary endpoint in the REMODEL studies.

Researchers also assessed several other measures of disease activity and progression.

These included the number of new or enlarging T2 brain lesions per year and the number of gadolinium-enhancing T1 lesions per scan.

The studies also measured serum neurofilament light chain, or sNfL, concentrations.

sNfL is a biomarker that can provide information about nerve damage and neurological disease activity.

Another important measure was the percentage of patients achieving no evidence of disease activity, known as NEDA-3.

Together, these measures are intended to provide a broader view of how a multiple sclerosis treatment affects inflammation, relapses and disability.

Novartis Plans Global Regulatory Submissions

Following the positive Phase III results, Novartis plans to seek regulatory approval for remibrutinib in RMS around the world.

The company will present detailed results from REMODEL-1 and REMODEL-2 as a late-breaker at MSToronto2026.

Novartis also intends to hold an investor call following the congress presentation.

The full clinical data will provide more detail about the size and consistency of the treatment effect, as well as the safety findings from the two trials.

Regulatory authorities will then evaluate the available evidence before deciding whether remibrutinib can be approved for RMS.

Remibrutinib Is Already Approved in Other Conditions

While its use in multiple sclerosis remains under investigation, remibrutinib has already been approved for another condition.

The 25 mg formulation was approved by the U.S. Food and Drug Administration in September 2025 and by the European Medicines Agency in April 2026 for adults with chronic spontaneous urticaria.

It is marketed as Rhapsido for this indication.

The approvals in chronic spontaneous urticaria provide clinical experience with the medicine, while the REMODEL program is evaluating whether it can offer a similar therapeutic benefit in multiple sclerosis.

Novartis Continues Its Focus on Neurology

Multiple sclerosis has been an important area of research for Novartis for decades.

The company has developed and supported several treatments for people living with MS and continues to investigate new approaches to neurological disease.

With remibrutinib, Novartis is expanding its research into neuroimmunology.

The company is also working across other areas of neuroscience, including neurodegeneration and neuromuscular diseases.

The broader remibrutinib development program includes studies in conditions such as hidradenitis suppurativa and food allergy.

For multiple sclerosis, the company is continuing to evaluate remibrutinib in RMS through the REMODEL program and in secondary progressive multiple sclerosis through the REMASTER study.

The Phase III REMODEL-1 and REMODEL-2 results now give Novartis additional clinical evidence as it prepares to discuss remibrutinib with regulatory authorities and works toward potential global approval for adults with relapsing multiple sclerosis.